ArticleThe Journal of experimental medicine2010
Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 200 citations in OpenAlex.
- Nanoparticles targeting liver sinusoidal endothelial cells improve tolerance to vector and transgene antigens through tolerance spreading.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- CD38 endows local antigen-specific TNature immunology · 2026Article
- Shaping death: how the microbiome regulates tumour cell demise and therapy response.Cancer metastasis reviews · 2026Review
- Regenerating myofiber with activating of TGF-β signaling contributes to macrophage efferocytosis through enhancing Tregs response in inflamed muscle.Frontiers in immunology · 2026Article
- Lipid Metabolism in Regulatory T Cells in Health and Disease.Journal of inflammation research · 2026Review
- Optimising Recovery of Hepatic Regulatory T Cells: A Practical Guide Using ARTC2 Blockade.European journal of immunology · 2025Article
- Modelling the ageing dependence of cancer evolutionary trajectories.Nature reviews. Cancer · 2025Review
- Purin Metabolism Is Crucial for Regulatory T Cell Stability and Function.European journal of immunology · 2025Review
- Macrophage expression of P2X7 controls autoimmune uveitis.Journal of neuroinflammation · 2025Article
- ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory T Cells in Intrarenal Inflammation.Journal of the American Society of Nephrology : JASN · 2025Article
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?Immune network · 2025Review
- ATP/P2X7 receptor signal aggravates ischemic stroke injury by activating Th17 cells via STAT3/IL-21 pathway.Frontiers in immunology · 2025Article
- CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus.Frontiers in immunology · 2025Article
- Cancer immunometabolism: advent, challenges, and perspective.Molecular cancer · 2024Review
- The P2X7 receptor in mucosal adaptive immunity.Purinergic signalling · 2024Review
- Administration of an AAV vector coding for a P2X7-blocking nanobody-based biologic ameliorates colitis in mice.Journal of nanobiotechnology · 2024Article
- Impact of NAD+ metabolism on ovarian aging.Immunity & ageing : I & A · 2023Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4(+)CD25(+)FoxP3(+) regulatory T cells (T reg cells) play a major role in the control of immune responses but the factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD(+)) released during cell damage or inflammation results in ART2.2-mediated ADP-ribosylation of the cytolytic P2X7 receptor on T cells. We show that T reg cells express the ART2.2 enzyme and high levels of P2X7 and that T reg cells can be depleted by intravenous injection of NAD(+). Moreover, lower T reg cell numbers are found in mice deficient for the NAD-hydrolase CD38 than in wild-type, P2X7-deficient, or ART2-deficient mice, indicating a role for extracellular NAD(+) in T reg cell homeostasis. Even routine cell preparation leads to release of NAD(+) in sufficient quantities to profoundly affect T reg cell viability, phenotype, and function. We demonstrate that T reg cells can be protected from the deleterious effects of NAD(+) by an inhibitory ART2.2-specific single domain antibody. Furthermore, selective depletion of T reg cells by systemic administration of NAD(+) can be used to promote an antitumor response in several mouse tumor models. Collectively, our data demonstrate that NAD(+) influences survival, phenotype, and function of T reg cells and provide proof of principle that acting on the ART2-P2X7 pathway represents a new strategy to manipulate T reg cells in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.